Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (6): 626-631.doi: 10.3736/jcim20080616

• Original Experimental Research • Previous Articles     Next Articles

Effects of Xiehuo Bushen Decoction on survival and differentiation of transplanted neural stem cells in brains of rats with intracerebral hemorrhage

Peng-cheng Zhong, Xing-qun Li(), Qing-hua Liang, Wen-fang Luo, Qing-er Liu, Jie-kun Luo, Tao Tang, Yuan Lin   

  1. Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China
  • Received:2007-09-29 Online:2008-06-20 Published:2008-06-15
  • Contact: LI Xing-qun

Objective: To investigate the effects of Xiehuo Bushen Decoction (XHBSD), a compound Chinese herbal medicine, on the survival and differentiation of transplanted neural stem cells (NSCs) in brains of rats with intracerebral hemorrhage, and to explore the mechanism of Xiehuo Bushen formula in promoting the survival of transplanted NSCs.
Methods: NSCs separated from hippocampuses of neonatal SD rats were cultured. Sixty-five panel reactive antibody (PRA) positive SD rats were selected by lymphocytotoxicity methods. The PRA positive rats were made into intracerebral hemorrhagic model and divided into three groups: cerebral hemorrhage group (n=15), NSCs transplanted group (n=25) and XHBSD group (n=25). XHBSD was orally administered after 5-bromodeoxyuridine (BrdU)-marked NSCs were transplanted in brains of rats with intracerebral hemorrhage in the XHBSD group. Rats in the other two groups were administered distilled water. The expressions of interferon gamma (IFN-γ) and interleukin-4 (IL-4) mRNAs were measured by reverse transcription polymerase chain reaction (RT-PCR); the numbers of BrdU and 200 kD neurofilament (NF200) positive cells were detected by double-labeling immunofluorescence method.
Results: The expression of IFN-γ mRNA was down-regulated significantly in the XHBSD group, but the expression of IL-4 mRNA was up-regulated significantly (P<0.05). The numbers of BrdU and NF200 positive cells were also increased remarkably in the XHBSD group.
Conclusion: XHBSD can promote the survival and differentiation of transplanted NSCs, which may be related to inducing the expression of IL-4 mRNA and inhibiting the expression of IFN-γ mRNA.

Key words: Xiehuo Bushen Decoction, neural stem cells, interferon gamma, interleukin-4, rats

CLC Number: 

  • R289.5

Figure 1

Nestin positive NSCs (Immunofluorescence staining, ×400)"

Figure 2

BrdU positive NSCs (Immunofluorescence staining, ×400)"

Figure 3

Caesar red staining positive lymphocytes (Inverted microscope, ×100) PRA value is about 80%. "

Figure 4

Expression of IFN-γ mRNA in XHBSD group at different time points"

Figure 5

Expression of IL-4 mRNA in XHBSD group at different time points"

Table 1

Expressions of IFN-γ and IL-4 mRNAs 2, 4 and 7 days after transplantation ($\bar{x}$±s)"

Group n IFN-γ mRNA IL-4 mRNA
2 days 4 days 7 days 2 days 4 days 7 days
Cerebral hemorrhage 15 0.73±0.01 0.65±0.01 0.63±0.03 0.91±0.12 0.92±0.02 0.94±0.13
NSCs transplanted 25 0.80±0.21* 0.67±0.02 0.65±0.12* 0.90±0.02* 0.89±0.11 0.90±0.05*
XHBSD 25 0.68±0.01** 0.63±0.01 0.59±0.01** 0.96±0.02 0.97±0.03 0.99±0.01*

Figure 6

BrdU and NF200 positive cells in XHBSD group and NSCs transplanted group 21 d after transplantation (Double immunofluorescent labeled staining, ×400) A: XHBSD group; B: NSCs transplanted group"

[1] Zhao CH. The principle, technology and clinic of stem cells[M]. Beijing: Chemical Industry Press, 2005: 112
赵春华 . 干细胞原理、技术与临床[M]. 北京: 化学工业出版社, 2005: 112
[2] Drukker M, Katz G, Urbach A , et al. Characterization of the expression of MHC proteins in human embryonic stem cells[J]. Proc Natl Acad Sci U S A, 2002,99(15):9864-9869
doi: 10.1073/pnas.142298299 pmid: 12114532
[3] Ostenfeld T, Caldwell MA, Prowse KR , et al. Human neural precursor cells express low levels of telomerase in vitro and show diminishing cell proliferation with extensive axonal outgrowth following transplantation[J]. Exp Neurol, 2000,164(1):215-226
doi: 10.1006/exnr.2000.7427
[4] Hu SH, Wu H, Liu AQ . The immunological characteristics of central nervous system and the problem of immunological rejection of neural stem cell transplantation[J]. Guo Ji Nao Xue Guan Bing Za Zhi, 2006,14(7):547-551
doi: 10.3760/cma.j.issn.1673-4165.2006.07.013
胡苏华, 武衡, 刘爱群 . 中枢神经系统的免疫学特性与神经干细胞移植的免疫排斥问题[J]. 国际脑血管病杂志, 2006,14(7):547-551
doi: 10.3760/cma.j.issn.1673-4165.2006.07.013
[5] Yang F, Wan Q . The problem in the clinical application of cell transplantation therapy[J]. Lin Chuang Shen Jing Bing Xue Za Zhi, 2006,19(2):158-159
杨芬, 万琪 . 细胞移植治疗临床应用所面临的问题[J]. 临床神经病学杂志, 2006,19(2):158-159
[6] Obata F, Yoshida K, Ohkubo M , et al. Contribution of CD4+ and CD8+ T cells and interferon-gamma to the progress of chronic rejection of kidney allografts: the Th1 response mediates both acute and chronic rejection[J]. Transpl Immunol, 2005,14(1):21-25
doi: 10.1016/j.trim.2004.11.003
[7] He XY, Verma N, Chen J , et al. IL-5 prolongs allograft survival by down regulating IL-2 and IFN-gamma cytokines[J]. Transplant Proc, 2001,33(1):703-704
doi: 10.1016/S0041-1345(00)02212-0 pmid: 11267027
[8] Ray J, Peterson DA, Schinstine M , et al. Proliferation, differentiation, and long-term culture of primary hippocampal neuron[J]. Proc Natl Acad Sci U S A, 1993,90(8):3602-3606
doi: 10.1073/pnas.90.8.3602 pmid: 8475109
[9] Duquesnoy RJ, Marrari M . Multilaboratory evaluation of serum analysis for HLA antibody and crossmatch reactivity by lymphocytotoxicity methods[J]. Arch Pathol Lab Med, 2003,127(2):149-156
[10] Hooper DK, Hawkins JA, Fuller TC , et al. Panel-reactive antibodies late after allograft implantation in children[J]. Ann Thorac Surg, 2005,79(2):641-644
doi: 10.1016/j.athoracsur.2004.07.052 pmid: 15680851
[11] Rosenberg GA, Mun-Bryce S, Wesley M , et al. Collagenase induced intracerebral hemorrhage in rats[J]. Stroke, 1990,21(5):801-807
doi: 10.1161/01.STR.21.5.801 pmid: 2160142
[12] Nonaka M, Yoshikawa M, Nishimura F , et al. Intraventricular transplantation of embryonic stem cell-derived neural stem cells in intracerebral hemorrhage rats[J]. Neurol Res, 2004,26(3):265-272
doi: 10.1179/016164104225014049
[13] Tang T, Li XQ, Wu H , et al. Activation of endogenous neural stem cells in experimental intracerebral hemorrhagic rat brains[J]. Chin Med J (Engl), 2004,117(9):1342-1347
doi: 10.1370/afm.226 pmid: 1537742622
[14] Kim JY, Kim D, Choi I , et al. MHC expression in a human adult stem cell line and its down-regulation by hCMV US gene transfection[J]. Int J Biochem Cell Biol, 2005,37(1):69-78
doi: 10.1016/j.biocel.2004.04.024
[15] Kuwatani M, Ikarashi Y, Iizuka A , et al. Modulation of acute graft-versus-host disease and chimerism after adoptive transfer of in vitro-expanded invariant Valpha14 natural killer T cells[J]. Immunol Lett, 2006,106(1):82-90
doi: 10.1016/j.imlet.2006.05.001
[16] Zhou GY. Principles of immunology[M]. Shanghai: Shanghai Scientific and Technical Literature Press, 2000: 155
周光炎 . 免疫学原理[M]. 上海: 上海科学技术文献出版社, 2000: 155
[1] Morufu Eyitayo Balogun, Elizabeth Enohnyaket Besong, Jacinta Nkechi Obimma, Ogochukwu Sophia Mbamalu, Fankou Serges Athanase Djobissie. Protective roles of Vigna subterranea (Bambara nut) in rats with aspirin-induced gastric mucosal injury. Journal of Integrative Medicine, 2018, 16(5): 342-349.
[2] Lucky Legbosi Nwidu, Raphael Ellis Teme. Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity. Journal of Integrative Medicine, 2018, 16(4): 263-272.
[3] Kylie Connolly, Douglas Jackson, Candice Pullen, Andrew Fenning. Alpha-adrenoceptor antagonism by Crassostrea gigas oyster extract inhibits noradrenaline-induced vascular contraction in Wistar rats. Journal of Integrative Medicine, 2015, 13(3): 194-200.
[4] Hussein O. B. Oloyede, Matthew C. Adaja, Taofeek O. Ajiboye, Musa O. Salawu. Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats. Journal of Integrative Medicine, 2015, 13(2): 105-114.
[5] Udhaya Lavinya Baskaran, Sherry Joseph Martin, Rasool Mahaboobkhan, Sabina Evan Prince. Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats. Journal of Integrative Medicine, 2015, 13(2): 115-121.
[6] Anirudha A. Lande, Shirishkumar D. Ambavade, Uma S. Swami, Prafulla P. Adkara Prashant D. Ambavade, Arun B. Waghamare. Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase. Journal of Integrative Medicine, 2015, 13(1): 25-33.
[7] Elizabeth Abidemi Balogun, Sylvia Orume Malomo, Joseph Oluwatope Adebayo, Ahmed Adebayo Ishola, Ayodele Olufemi Soladoye, Lawrence Aderemi Olatunji, Olatunji Matthew Kolawole, Stephen Olubunmi Oguntoye, Abiola Samuel Babatunde, Oluwole Busayo Akinola . In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre. Journal of Integrative Medicine, 2014, 12(6): 504-511.
[8] Xin-fang Zhang, Ji Zhu, Wen-ye Geng, Shu-jun Zhao, Chuan-wei Jiang, Sheng-rong Cai, Miao Cheng, Chuan-yun Zhou, Zi-bing Liu. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease. Journal of Integrative Medicine, 2014, 12(5): 417-424.
[9] Urmila Aswar, Mayuri Gurav, Ganesh More, Khaled Rashed, Manoj Aswar. Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats. Journal of Integrative Medicine, 2014, 12(5): 439-446.
[10] Benjamin Perry, Junzeng Zhang, Tarek Saleh, Yanwen Wang. Liuwei Dihuang, a traditional Chinese herbal formula, suppresses chronic inflammation and oxidative stress in obese rats. Journal of Integrative Medicine, 2014, 12(5): 447-454.
[11] Upendarrao Golla, Praveen Kumar Gajam, Solomon Sunder Bhimathati. Evaluation of diuretic and laxative activity of hydro-alcoholic extract of Desmostachya bipinnata (L.) Stapf in rats. Journal of Integrative Medicine, 2014, 12(4): 372-378.
[12] Qian Zhang, Xin-hua Xiao, Ming Li, Wen-hui Li, Miao Yu, Hua-bing Zhang, Fan Ping, Zhi-xin Wang, Jia Zheng ​. Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats. Journal of Integrative Medicine, 2014, 12(3): 162-170.
[13] Amir Rashidian​, Saeed Mehrzadi, Ali Reza Ghannadi, Parvin Mahzooni, Samira Sadr, Mohsen Minaiyan​. Protective effect of ginger volatile oil against acetic acid-induced colitis in rats: A light microscopic evaluation. Journal of Integrative Medicine, 2014, 12(2): 115-120.
[14] Dilpesh Jain​, Manish Kumar Bansal, Rahul Dalvi​, Aman Upganlawar​, Rahul Somani​. Protective effect of diosmin against diabetic neuropathy in experimental rats. Journal of Integrative Medicine, 2014, 12(1): 35-41.
[15] Manjusha Choudhary​, Vipin Kumar​, Surender Singh​. Gastric antisecretory and cytoprotective effects of hydroalcoholic extracts of Plumeria alba Linn. leaves in rats. Journal of Integrative Medicine, 2014, 12(1): 42-51.
Full text



[1] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[2] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[3] Wei Zhang, Xiang-feng Lu, Xiao-mei Zhang, Jian-jun Wu, Liang-duo Jiang. A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation. Journal of Chinese Integrative Medicine, 2008, 6(1): 60-67
[4] Bo Wang , Wei Yan , Li-hui Hou, Xiao-ke Wu. Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients with polycystic ovary syndrome. Journal of Chinese Integrative Medicine, 2010, 8(11): 1018-1022
[5] Hui-min Liu, Xian-bo Wang, Yu-juan Chang, Li-li Gu. Systematic review and meta-analysis of randomized controlled trials of integrative medicine therapy for treatment of chronic severe hepatitis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1211-1228
[6] Liang-ping Hu, Xiao-lei Bao. Three-factor designs unable to examine the interactions (Part 2). Journal of Chinese Integrative Medicine, 2012, 10(11): 1229-1232
[7] Pedro Saganha João, Doenitz Christoph, Greten Tobias, Efferth Thomas, J. Greten Henry. Qigong therapy for physiotherapists suffering from burnout: a preliminary study. Journal of Chinese Integrative Medicine, 2012, 10(11): 1233-1239
[8] Ming-qing Wei , Jin-zhou Tian , Jing Shi , Fu-yun Ma , Ying-chun Miao , Yong-yan Wang. Effects of Chinese medicine for promoting blood circulation and removing blood stasis in treating patients with mild to moderate vascular dementia: a randomized, double-blind and parallel-controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(11): 1240-1246
[9] Nian-hong Wang , Jun-tao Yan , Wu-quan Sun , Yong-shan Hu , Jun Xia , Li-cheng Wei , Jie Jia , Gui-lin Ouyang , Yong He , Yan-ming Guo , Jie Xu . Effects of early application of Tuina treatment on quadriceps surface myoelectricity in patients after total knee arthroplasty: a randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(11): 1247-1253
[10] Xiao Zhang , Bing-bing Ning , Shuang Ren , Li-jun Zhang , Wen-meng Zhang , Jia-mei Chen , Gao-feng Chen , Hua Zhang , Yong-ping Mu , Ping Liu. Effects of Chinese herbal medicine Xiaopi Pill in preventing rats from dimethylnitrosamine-induced liver fibrosis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1286-1292